Our earlier studies have established that galanin (GAL) is an important neuromodulator involved in the regulation of gonadal functions. The actions of GAL are exerted at different levels in the hypothalamic-pituitary-gonadal axis. GAL stimulates LHRH secretion from arcuate nucleus-median eminence (AN-ME) fragments incubated in vitro, requiring a functional noradrenergic.system. It is also able to stimulate LH secretion and enhance LHRH-induced LH release by acting directly at the level of the anterior pituitary gland. Since GAL is secreted into the hypophyseal portal circulation in higher concentrations than those observed in peripheral blood, the peptide should be considered as a member of the hypothalamic hormone family. During the past year, we have explored whether endogenous GAL regulates physiological events as well as aspects of the regulation of hypothalamic secretion of GAL. We have demonstrated that endogenous GAL is involved in the mechanisms which lead to the origination of the preovulatory surges of LH and PRL. In addition, we developed an incubation protocol which enables us to measure GAL release from AN-ME in vitro and to evaluate the role of several classical neurotransmitters on GAL release. In initial studies aimed to establish this incubation protocol, we observed that GAL release from AN-ME, but not from ME fragments, presented a release time-course consisting of an exponential increasing phase followed by a plateau releasing period. This indicated that GAL accumulating in the incubation medium could stop the release of the peptide. In collaboration with Drs. Merchenthaler and Liposits, we initiated a series of experiments designed to evaluate whether GAL neurons within the AN could be connected between them for regulating their own release rate. As a result, we have shown the existence of a functional galaninergic network located in the AN, which can regulate its own firing activity via a negative ultrashortloop feedback mechanism. Therefore, our studies have shown that GAL, a peptide first discovered in the gut, constitutes a hypothalamic hypophysiotropic hormone which has a physiological role in the regulation of reproductive functions.